CLIC4 regulates apical exocytosis and renal tube luminogenesis through retromer- and actin-mediated endocytic trafficking
| Autor: | Guo An He, Celine Yeh, Wataru Otsu, Yun Cin Luo, Kuo-Shun Hsu, Syed S. Shehab, Aihao Ding, Diane Felsen, Jen-Zen Chuang, Dix P. Poppas, Ya Chu Hsu, Ching-Hwa Sung, Szu Yi Chou, Jie Chen, Michael B. Marean, Vincent Shieh |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Retromer Endosome Science Endocytic cycle General Physics and Astronomy Endosomes General Biochemistry Genetics and Molecular Biology Exocytosis Article Madin Darby Canine Kidney Cells Mitochondrial Proteins 03 medical and health sciences Mice Dogs Chloride Channels CLIC4 medicine Animals Immunoprecipitation Mice Knockout Multidisciplinary biology General Chemistry Apical membrane Microvillus Actins Transport protein Cell biology Protein Transport 030104 developmental biology medicine.anatomical_structure biology.protein |
| Zdroj: | Nature Communications Nature Communications, Vol 7, Iss 1, Pp 1-14 (2016) |
| ISSN: | 2041-1723 |
| Popis: | Chloride intracellular channel 4 (CLIC4) is a mammalian homologue of EXC-4 whose mutation is associated with cystic excretory canals in nematodes. Here we show that CLIC4-null mouse embryos exhibit impaired renal tubulogenesis. In both developing and developed kidneys, CLIC4 is specifically enriched in the proximal tubule epithelial cells, in which CLIC4 is important for luminal delivery, microvillus morphogenesis, and endolysosomal biogenesis. Adult CLIC4-null proximal tubules display aberrant dilation. In MDCK 3D cultures, CLIC4 is expressed on early endosome, recycling endosome and apical transport carriers before reaching its steady-state apical membrane localization in mature lumen. CLIC4 suppression causes impaired apical vesicle coalescence and central lumen formation, a phenotype that can be rescued by Rab8 and Cdc42. Furthermore, we show that retromer- and branched actin-mediated trafficking on early endosome regulates apical delivery during early luminogenesis. CLIC4 selectively modulates retromer-mediated apical transport by negatively regulating the formation of branched actin on early endosomes. Chloride intracellular channel (CLIC) 4 is an ion channel, localized in the cytoplasm, and first identified as an actin binding protein. Here, Chou et al. knockout CLIC4 in mice and observe tubulogenesis and renal proximal tubule dilation defects, which is caused by irregular actin and endosomal trafficking. |
| Databáze: | OpenAIRE |
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